Studies this year have centered on the pathophysiology of Legdig cell activation in patients with familial precocious puberty. This interesting group of patients demonstrate what appears to be gonadotropin independent Leydig cell activity. Previous studies have focused on the possibility that a humoral factor is responsible for this process. Several groups have searched for this hypothetical factor using in vitro assays of Leydig cell function, usually the dispersed rat Leydig cell assay. These systems have failed to reveal Leydig cell stimulators. We reasoned that the heterologous nature of the assay system might explain the failure to detect such substances. We examined this hypothesis by infusing plasma from patients with the disorder and from pubertal stage matched controls directly into the spermatic artery of rhesus monkeys. Testosterone secretion into the testicular vein served as the response parameter. This system separated the precocious puberty group from the other two, supporting the hypothesis that a circulating factor may play a role in the pathogenesis of this syndrome.